Prematurity: Clinical Issuesnorthpugetsoundpec.org/wp-content/.../2012/03/...2.pdfMar 05, 2012 · Neofax 2011 Fluid & Electrolyte Management Fluid requirements (May be much higher

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Prematurity: Clinical Issues Part Two

Liz Graf-Brennen, RNC, MSNeonatal C.N.S.

Swedish Medical Center

Birthweight: 2 ½ lbs

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Neurological

The third trimester is a time of rapid brain growth and development which continues on through the first year.

36 weeks

32 weeks28 weeks

Neurological

� Cortical neurons are generated in the periventricular germinal matrix.

� Almost all neurons have actually been generated by 25 weeks.

Neurological

� Neurons then migrate out towards the surface of the cortex, branch out, and form synapses.

� By 32-34 weeks, focus of development shifts to the cortex

� Germinal matrix tissues themselves undergo involution.

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Neurological: Hemorrhage

At 24-28 weeks, the supportive structures around the germinal matrix are still very fragile, making the baby vulnerable to hemorrhage into the ventricles.

Neurological

The autonomic control of cerebral blood flow is poorly developed in the preemie, allowing fluctuations in cerebral blood flow which can lead to bleeding and/or ischemia.

Intraventricular Hemorrhage (IVH)

� Risk Factors :� <34 weeks� <1500 grams� “unstable”

� Incidence:� Has decreased over the past 20 years to

about 10-20% of VLBW babies in most NICUs. (Down from over 50%)


� Clinical Presentation:� Ranges from catastrophic (least

common) to silent (most common)

� Risk period: first 3-4 days of life

� Diagnosis: � Cranial Ultrasound at 1 week of age

detects 95% of all IVH.

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� Management� Serial ultrasounds� CSF taps or drainage for progressive

hydrocephalus� Ventricular-peritoneal shunt


� Prognosis� Neurodevelopmental outcome of

preemies with grade I or II hemorrhage similar to comparable babies with no hemorrhage.

� Some increased risk in visual motor integration skills.

Intraventricular Hemorrhage (IVH)� 30-40% of those with moderate

(Grade III ) bleeds have major neurologic sequelae (higher with periventricular infarct or PVL)

� “Major” neurologic sequelae� Blindness� Deafness� Cerebral Palsy� Severe mental retardation

Periventricular Leukomalacia (PVL)

� Necrosis of white matter in a characteristic distribution dorsal and lateral to the lateral ventricles. It is the primary ischemic lesion of the premature infant.

� Currently the major form of brain injury in preterm infants.

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� Risk Factors� Prematurity – 23-32 weeks� Postnatal illness – hypoxia,

ischemia, inflammation

Periventricular LeukomalaciaPathophysiology� Pressure passive cerebral circulation� Rapidly growing cerebral white matter

has high metabolic needs� Periventricular vascular anatomic

factors� Low blood flow leading to necrosis,

hemorrhage, and cysts� Initial insult plus damage to process of

myelinization


� Clinical Presentation� Generally silent, picked up on ultrasound.

Delay before evident on ultrasound.

� Prognosis� Major long term sequela is spastic

diplegia, especially affecting legs. � High risk for developmental problems.


ventricle

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Diffuse Cellular PVL

� MRI can detect diffuse PVL on cellular level.

� May play a role in intellectual deficit.

� Stable BP and oxygenation

� Maintain good glucose levels

� Avoid rapid infusion of bicarb

� Avoid low pCO2 levels

� Gentle handling, developmental support

Neuroprotective Strategies:

Retinopathy of Prematurity (ROP)

Retinopathy of Prematurity (ROP)

� ROP describes an abnormality of growth and development of the retina of the premature infant.

� Untreated, it may progress to retinal detachment and blindness.

� In the US, approximately 500 to 700 infants lose their vision due to ROP each year.� Additionally, 4500 infants will develop

complications of ROP including myopia, strabismus, and late-onset retinal detachment/blindness.

Normal Retinal Development

� The retina begins to develop at the 16th week of gestation.

� Blood vessels grow out of the optic disc and slowly advance outward.

� The retina is not completely vascularizeduntil 36 to 40 weeks gestation.

� Preterm infant has immature formation of antioxidant enzymes and free radical scavengers.

Pathophysiology of ROP� Initial hyperoxic injury

� Elevated oxygen levels (oxygen saturations >95%) cause severe vasoconstriction and destruction of immature retinal vessels

� The vasoconstriction severely inhibits blood flow to the retina (retinal ischemia)

� By about 30-34 weeks gestation the ischemic retina attempts to restore its blood flow by releasing growth factors to stimulate new blood vessel growth (neovascularization)� This “catch-up” growth is abnormal and poorly controlled ,

and may result in retinal detachment and blindness.

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Pathophysiology of ROP

Hyperoxia (high O2 saturations)Vessel constriction/destruction

Neovascularization(abnormal vessel growth)

ROP: Prevention

�Avoid hyperoxia (O2 sat >95%), especially in the first few weeks of life

�Avoid large fluctuations in oxygen saturations

� 30 weeks or less at birth� <1500 grams at birth� Consider screening if premature,

1500-1800 grams at birth, and unstable

� Start 4 to 6 weeks after birth at 31 to 33 weeks corrected gestational age.

(AAP Guideline April 2006-rev. Sept 2006)

Retinopathy of Prematurity(ROP): Screening Guidelines

Stage 1 : Demarcation Line Stage 2: Ridge

Stage 3: Ridge with ExtraretinalVascular Proliferation

Plus Disease: Dilated & Tortuous Vessels

Stages of ROP: Stage 4

Stage 4:Stage 4:

Subtotal retinal Subtotal retinal detachment beginning at detachment beginning at the ridge. the ridge.

The retina is pulled The retina is pulled anteriorlyanteriorly into the vitreous into the vitreous by the by the fibrovascularfibrovascular ridge. ridge.

http://www.nei.nih.gov/rop/images/ROP10-31-03.mpeg

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Laser Surgery

Laser photocoagulation/retinal ablation has been successfully used to prevent retinal detachment in threshold ROP.

� Zone 1 ROP: any stage with plus disease

� Zone 1 ROP: stage 3 – no plus disease

� Zone II: stage 2 or 3 with plus disease

Retinopathy of Prematurity (ROP) – Laser Treatment Guidelines

Emerging Therapy:Intravitreal Bevacizumab (Avastin)

� 2011 Study showed benefit for vision threatening ROP in Zone 1

� Anti-VEGF agent (vascular

endothelial growth factor)

Mintz-Hitner, H (2011) NEMJ 364(7) p.603

VON presentation Dec. 2011

OutcomeMild ROP (Stage 2 or

less) generally has a

favorable outcome.

Severe ROP (Stage 3

and above) may

progress to partial or

total retinal detachment

and blindness.

Infants with severe ROP are

also at risk for severe myopia

(near-sightedness) and strabismus/amblyopia

Infants with severe ROP may have

retinal scarring which can lead to late

retinal detachments in adolescence or early adulthood

Hematological: Anemia

� Acute (pathologic)� bruising, hemorrhage, or hemolysis

� Iatrogenic Anemia from lab testing

� Survival of premature infant’s red blood cells about 50% less than adult circulation time. (Adult cells last average of 120 days)

TransfusionInfant Protocol

� Puget Sound Blood Center Infant 0-4 month Protocol uses specimen of infant or cord blood for type and antibody screen. This screen is good until infant is 4 months old (when they begin to make significant antibody of their own) or leaves hospital.

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TransfusionAssigned Aliquots

� Pediatric Assigned Unit � 1 Adult unit divided into 8 aliquots and

kept for that baby. � Reduces exposure to multiple donors� All units leukoreduced and irradiated� Good for 42 days from collection

Anemia of Prematurity

Physiologic� At birth, the infant is suddenly transferred from

the relative hypoxia of the uterus to the oxygen rich environment of the outside atmosphere.

� Red cell production in the bone marrow virtually ceases and resumes activity when the infant is about 2 months old.

� In the preterm infant, this physiologic process can be prolonged and the hematocrit fall to a lower level.


� Management� Premature infants on breast milk only need

supplemental iron once on full oral feedings to ensure they have iron when they begin reticulating.


� Management� Consider transfusion if infant has hematocrit

in low 20’s or teens, has apnea or oxygen needs, is not growing well, or has low reticulocyte count.

� Erythropoetin in limited situations

� Works slowly� Needs adequate iron stores

Hematological: Hyperbilirubinemia

� The preterm infant liver is immature and does not clear bilirubin as efficiently.

� Concern that immaturity of the blood/brain barrier makes preemie more vulnerable to bilirubin toxicity.

Hyperbilirubinemia

� Preemies generally treated for hyperbilirubinemia at lower levels than term infants.

� Exact levels are controversial, but the 2004 AAP guidelines show that even the mildly premature infant is at increased risk.

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Copyright ©2004 American Academy of Pediatrics

Subcommittee on Hyperbilirubinemia, Pediatrics 2004;114:297-316

Hyperbilirubinemia

� Late preterm infant at risk due to� immaturity of liver� immaturity of feeding skills� early discharge home without

adequate understanding and supervision.

webmd.com

Fluids & Electrolytes

� Newborn babies have high total body water content

� Neonates have higher basic metabolic rate� Newborn water requirements are 4-5 times

greater


� All newborns lose fluid after birth. � Loss of fluid from extracellular compartment

followed by diuresis, and weight loss� NNB regains weight as muscle and fat� This process complicated in preterm infants� More dilute urine, greater sodium and water

losses� Fluid overload may contribute to respiratory

distress, congestive heart failure, necrotizing enterocolitis, PDA

Immature Kidneys

� Newborns have a lower renal blood flowthan adults� increases rapidly after birth in the term and

older premature with postnatal shifts in blood flow

� more slowly in the preterm less than 34-35 weeks. (Remember: mom was doing this!)

� Newborn has lower glomerular filtration rate ; again, it doubles by two weeks of age, but increases more slowly in the younger preemie.

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Renal� Newborns have limited ability to

concentrate urine, and prematures are even more limited in this regard. Lose salt and water in urine.

� Full complement of nephrons develops at around 35 weeks.

� Postnatal renal function is more related to postbirth age than gestational age; birth stimulates some maturation.

Renal: Preterm Problems� Narrow margin of safety in calculating and

administering fluids and electrolytes.

� Fluid and Electrolyte Problems: Vulnerable to overhydration, dehydration, hyper/hyponatremia, hypo/hyperkalemia.

� Buffering Capacity: The preterm infant is vulnerable to any event that causes acidosis or alkalosis. They do not retain bicarb well.

Renal: Preterm Problems

� Drug Clearance:

� Prematurity and illness restrict a neonate’s ability to excrete certain drugs and increase risk of toxicity. Aminoglycosides in particular are timed with regard to gestational age and levels are followed.

Gentamicin

Neofax 2011

Fluid & Electrolyte Management� Fluid requirements� (May be much higher for the extremely

low birthweight without humidity)Day 1 80 cc/Kg/dayDay 2 80-100 cc/Kg/dayDay 3 100-120 cc/Kg/dayDay 4 120-150 cc/Kg/day

� Adjust baseline for insensible water loss such as phototherapy, radiant warmer, surgical conditions, immature skin

Fluid & Electrolyte Management

� Electrolytes added once the baby voids

� Strict monitoring of intake and output until stable

� Monitor electrolytes, pH, and blood gases.

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� Fluid status is assessed based on I&O, daily weight, appearance, and electrolytes (mainly Na +)

� Normal electrolyte values:Na+ 135-145K 3.5-5.5Cl 90-110

Gastrointestinal/Nutritional

One way out of NICU:

Grow, Baby, Grow!


� Immature GI tract function until 36-40 weeks limits digestion and absorption.

� GI motility is decreased in preterm infants

� Lower production of digestive and hepatic enzymes


� Maintaining Adequate Nutrition� Preterm infants are born without the

reserves of fat, carbohydrate, vitamins and minerals which would have been transferred from their mothers during the latter part of pregnancy.


� Maintaining Adequate Nutrition� Higher energy expenditure than in

the womb� Caloric needs related to the disease

processes � Developmentally, high caloric needs

for growth.

Growth & Nutrition

� Many premature infants born on lower end of growth curve.

� With inadequate nutrition, they tend to fall even lower on the curve.

� Inadequate nutrition leads to growth failure and impaired neurocognitivedevelopment

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� The Challenge of Catch-up Growth� Most VLBW infants regain birthweight by

2nd or 3 rd week of life. The longer the time it takes to regain, the slower the catchup growth will be.


� Goals for Growth:� To approximate in utero growth of a normal

fetus of the same postconceptual age

� Weight gain of 18 grams/kg/day

� Length: about .75 cm per week

� Head circumference: about .5 cm per week

Protein needs

� Parenteral nutrition now started within 24 hours of birth

� Trend is to start enteral nutrition earlier than in the past and be more aggressive in enteral feeding advancement

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Recommended Protein Intake

3.2-3.63.5-4.0Weight 1000-1800 gm

3.6-4.14.0-4.5Weight <1000 gm

g/100 kcalg/Kg/day

European Society for Pediatric Gastroenterology, Hepatology and Nutrition

2010

Options for Feeding

1. Preterm human milk2. Premature formula or fortified

breastmilk3. Fortification beyond the 24

calories4. Post-premature formula5. Extremely low birthweight babies

Selecting appropriate feeding:

� Preterm Human Milk is specially suited to the preterm infant’s higher protein and calorie needs for the first two to four weeks.

Selecting appropriate feeding:

� Preterm infant born less than 1800 grams get premature formula or fortified breast milk once they are on full feeding volume.

� Designed to be used until the infant reaches 2000-2500 grams body weight. (Use past that weight puts the infant at risk for toxicity of fat soluble vitamins.)

Fortification:� Many preemies need fortification beyond the

24 calories in premature formulas in order to achieve adequate weight gain.

� Various ways to do this depend on:� Baby’s clinical situation� Hospital formula contract� Local availability of products after DC.

� Call nutritionist at Level III center for questions.

Post-premature formula

� If the infant is formula feeding, both formula companies make 22-calorie formulas that are higher in protein, vitamins and minerals than standard formula, but not as rich as premature formulas.

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ELBW Infants

� The extremely low birthweight infant (ELBW, < 1000 grams) poses a challenge for bone mineralization, and some of these babies have been found to have fractures later if exclusively breastfed. Nutritionists recommend some fortification for them through the first year of life.

Gastrointestinal/Nutritional:Feeding Intolerance

� May be mild and respond to nursing measures or serious and require medical intervention

Feeding Intolerance

� Signs and Symptoms:� Residuals: Current thinking is to

tolerate up to 50% of previous feed if no associated GI symptoms.

� Emesis� Abdominal distension� Diarrhea� Increased apnea and/or bradycardia

The Fear: NECNecrotizing Enterocolitis

Gastrointestinal/Nutritional:Necrotizing Enterocolitis (NEC)

�NEC is an idiopathic disorder characterized by inflammation and necrosis of the mucosal layers of the gastrointestinal tract.

�Any part of the bowel can be affected, but most often the distal ileum and proximal colon are involved.

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Necrotizing Enterocolitis (NEC)

� What causes NEC?� We still do not know for sure. The

etiology has been debated and researched for many years.

� Some ischemic or hypoxic insult to gut?

� Bacteria involved� Indomethacin?


� Who is at risk for NEC?� Prematurity is the greatest risk factor.� Smaller babies born weighing less

than 1500 grams make up 70% of cases, but it can happen to a term infant

� 90-95% have been fed


� Signs and Symptoms� Feeding Intolerance

� Abdominal Distension� Visible Loops of Bowel� Blood in Stool� Gastric Residuals� Vomiting


� Signs and Symptoms� General systemic signs

� Lethargy� Apnea/bradycardia� Temperature instability� Hypotension/hypoperfusion


� Signs and Symptoms� Evidence of peritonitis

� Erythema or discoloration � Abdominal tenderness

� Can move very fast! Any of these signs warrant a careful look for others!


� Diagnostic Tests� X-Ray

� Dilated bowel loops with thickened walls due to local edema

� Pneumatosis intestinalis occurs when gas-forming bacteria invade the intestinal wall (diagnostic of NEC)

� Pneumoperitoneum occurs with bowel perforation

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pneumatosis

Pneumoperitoneum –free air in abdomen


� Diagnostic Tests� Blood culture� CBC� electrolytes


� Medical Management� NPO for bowel rest (often for 7-10 days)� Gastric decompression� Antibiotics� Serial X-Rays� Careful monitoring of blood glucose levels


� Medical Management� Respiratory support and correction of

acidosis� Circulatory support for hypotension:

hydration and inotropes� Blood components to correct

thrombocytopenia and DIC� Pain management


� Surgical Management� Resection of necrotic bowel� Creation of a stoma if necessary� Drain

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� Prevention� Prevent prematurity� Careful infection control, as NEC

does occur in clusters� Encourage pumping and

breastfeeding, as antibodies in breast milk provide some protection.


� Prevention� Various philosophies exist around

feeding practices� Delaying feedings delays NEC, but

does not prevent it� Excessive volume or rapid

advancement of feeding may be the critical factors rather than early feeding.


� Prevention� Slow advancement of feeding volumes is

probably the best approach, although there is no uniform standard

� One cautious approach recommended in the literature is to initiate small volume feedings and advance in increments of not > 20 cc/Kg/day

� Any advancement protocol better than none

Gavage: Indwelling Catheter

� Courtesy Neonatal Network

Gavage Feeding� Soft indwelling 5 or 6 Fr. Silicone

catheter� Orogastric vs. nasogastric tubes� For safety, enteral tubings should not be

physically compatible with IV connections (JCAHO Sentinel Event Alert)

� Can be left in to complete feeds of infants who are learning to nipple

Feeding Tolerance Algorithm

•Check gastric residual volume (GRV) prior to feed

•A large GRV is defined as

•If on TROPHIC feeds: 100% of the scheduled feeding volume (over 4 hours)

•If beyond trophic feeds: >50% of the scheduled feeding volume

Large or Green GRV

Perform physical exam/chart review and evaluate for:

•Abdominal distension · Emesis

•Increased apnea ·Dark green material

•Increased O2 requirement

•Temp instability

PE Normal PE Abnormal

• MD/ARNP Evaluation to consider

• Holding 1 feed & reevaluate, or make the infant NPO

• Serial reevaluations of exam/clinical course

• KUB

• Sepsis evaluation

•Refeed residual and give the full next feeding

•Check feeding tube placement (especially if green) by physical exam or radiograph

•Place infant in right lateral decubitus position

•Check stool frequency: consider glycerin per rectum

Persistent Large GRV

(>=3 in 24 hours) with normal PE

•Call MD/ARNP to consider:

•Holding one feed, & reducing feeding volume by 20% (maintain volume if on trophic feeds)

•Re-evaluating at next feed

•Obtaining KUB

•Considering feeds on pump

Not Large or Green GRV

Refeed and give full feed

For dark green emesis, always call

MD/ARNP

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Progression to Oral Feeding

� Evidence Based Approaches:� Breast Only� Step-wise

� Cue-Based – current trend

� A consistent institutional guideline helps parents, nurses, and babies

Progression to Oral Feeding

� Bottle feeding usually plays a role in getting a preemie to full oral feeding so they can go home, especially if mother cannot be in the hospital round the clock.

� Also important because of need for continued fortification.

Courtesy Children’s Medical Ventures

Nipple Feeding: What makes it hard for a premie?

� weaker muscle tone� lack flexion� absent or reduced sucking pads� few opportunities for positive oral

sensation� absent or immature reflexes� limited energy stores

Nipple Feeding: Enhancing Success

� quiet environment� watch for appropriate infant state� time� frequent burping/pacing� flow/nipple choice� positioning - support flexion� Good breastfeeding support and a

plan for the transition home

Techniques that Take the Initiative Away from the Baby

� Twisting/turning the bottle� Moving nipple up/down� Moving nipple in/out of baby’s mouth� Massaging chin or stimulating the

face

Tiny Miracles

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Discharge/Followup Issues

Beaumont Children’s Hospital

Remember: Day of discharge almost as stressful as admission. Don’t leave teaching til last day!!


� Do you have a followup pediatrician?!

� Infant safety & CPR class

� Immunizations, on same schedule as term infants


ROP Exams � Communication about follow-up

extremely important


� Car Seat Test recommended by AAP for infants born at less than 37 weeks

gestational age or 2500 grams

Car Seat Test – 2009 AAP Revised Guidelines

� 90 – 120 min or duration of travel time� Advise parents to use car seat for travel only

� Advises monitoring in car bed if that is used� Crash protection of car seats better

documented than that of car beds� Advises considering retesting before

transition to car seat from bed

� Avoid similar upright equipment like swings, infant seat, carriers until baby is larger

Pediatrics Vol 123, #5, May 2009


� Bed flat before baby goes home� No sheepskins or fluffy bedding� BUT, they need play time on their

tummy while they are awake!

“Back to Sleep”unless otherwise

ordered

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Discharge/Followup Issues� Susceptibility to RSV

� Teach parents to wash hands and protect baby from smoke and people with colds.

Discharge/Followup IssuesSynagis Criteria – 2009 revisions� Less than 2 years old:

� Requiring medical therapy for chronic lung disease or significant congenital heart disease

� Less than 1 year old:� Born at or before 28 weeks gestation� Congenital airway anomaly or neuromuscular

disease� Less than 6 months old at start of season

� Born before 32 weeks gestation� 32-35 weeks (“less than 35 weeks”) at birth with ri sk

factors: daycare or siblings under 5 years old –Synagis only for first 3 months

2009 Red Book AAP

Hearing Screen :All babies who have been in intensive care are at increased risk.

• Make sure they get their hearing screen before discharge

• Increased incidence of both sensorineural and conductive hearing loss

• Hearing loss occurs both in the newborn period and during the first year


� High Risk Followup Clinic� VLBW (<1250 grams)� 30 weeks gestational age or less� Bronchopulmonary dysplasia/significant

mechanical ventilation� CNS complications: IVH, PVL, seizures,

meningitis� Prenatal drug exposure


� Feeding Plan / Growth Monitoring

� See gaining and growing website:� http://depts.washington.edu/growing

You’ve done your job! Let go and rest!

Documents

Prematurity: Clinical Issuesnorthpugetsoundpec.org/wp-content/.../2012/03/...2.pdfMar 05, 2012 · Neofax 2011 Fluid & Electrolyte Management Fluid requirements (May be much higher